The antibiotic thienamycin is perhaps the best known member of the new family of antibiotics generically designated 1-carbapen-2-em-3-carboxylic acids. Derivatives of thienamycin, which were originally discovered on working with the natural product, are also well known. One of these, N-formimidoyl thienamycin (3), has been studied extensively: ##STR2## Because of the intrinsic instability of thienamycin, the preparation of 3 from thienamycin cannot be described as efficient since a variable but appreciable quantity of the starting thienamycin is lost in the process. The present invention relates to a process for the preparation of N-formimidoyl-2-aminoethanethiol and N-protected-N-formimidoyl-2-aminoethanethiols (2) which are useful in the preparation of N-formimidoyl thienamycin. ##STR3## wherein R.sup.2 is hydrogen or a protecting group.
The present invention also relates to a very efficient process for the direct synthesis of N-formimidoyl thienamycin (3) from the activated keto ester 1 on reaction with displacing agent 2 followed by hydrogenation: ##STR4## wherein R.sup.1 and R.sup.2 are protecting groups; and X is a leaving group. Details of this scheme, including preferred values for R.sup.1 and R.sup.2 are given below. It should be noted that step 1.fwdarw.1a is known; see European patent application No. 79101307.1 Publication No. 0007973/A1 (Feb. 20, 1980). Steps 1a.fwdarw.1b.fwdarw.3 are known in analogy to the synthesis of thienamycin and to that extent the cited European patent application is incorporated herein by reference.